BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a progressive or relapsing and remitting paralysing illness, probably due to an autoimmune response, which should benefit from corticosteroid treatment. Non-randomised studies suggest that corticosteroids are beneficial. Two commonly used corticosteroids are prednisone and prednisolone. Both are usually given as oral tablets. Prednisone is converted into prednisolone in the liver so that the effect of the two drugs is usually the same. Another corticosteroid, dexamethasone, is more potent and is used in smaller doses. The review was first published in 2001 and last updated in 2015; we undertook this update to identify any new evidence.
OBJECTIVES: To assess the effects of corticosteroid treatment for CIDP compared to placebo or no treatment, and to compare the effects of different corticosteroid regimens.
SEARCH METHODS: On 8 November 2016, we searched the Cochrane Neuromuscular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for randomised trials of corticosteroids for CIDP. We searched clinical trials registries for ongoing trials.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs of treatment with any corticosteroid or adrenocorticotrophic hormone for CIDP, diagnosed by an internationally accepted definition.
DATA COLLECTION AND ANALYSIS: Two authors extracted data from included studies and assessed the risk of bias independently. The intended primary outcome was change in disability, with change in impairment after 12 weeks and side effects as secondary outcomes. We assessed strength of evidence using the GRADE approach.
MAIN RESULTS: One non-blinded RCT comparing prednisone with no treatment in 35 eligible participants did not measure the primary outcome for this systematic review. The trial had a high risk of bias. Neuropathy Impairment Scale scores after 12 weeks improved in 12 of 19 participants randomised to prednisone, compared with five of 16 participants randomised to no treatment (risk ratio (RR) for improvement 2.02 (95% confidence interval (CI) 0.90 to 4.52; very low-quality evidence). The trial did not report side effects in detail, but one prednisone-treated participant died.A double-blind RCT comparing daily standard-dose oral prednisolone with monthly high-dose oral dexamethasone in 40 participants reported none of the prespecified outcomes for this review. The trial had a low risk of bias, but the quality of evidence was limited as it came from a single small study. There was little or no difference in number of participants who achieved remission (RR 1.11; 95% CI 0.50 to 2.45 in favour of monthly dexamethasone; moderate-quality evidence), or change in disability or impairment after one year (low-quality evidence). Change of grip strength or Medical Research Council (MRC) scores demonstrated little or no difference between groups (moderate-quality to low-quality evidence). Eight of 16 people in the prednisolone group and seven of 24 people in the dexamethasone group deteriorated. Side effects were similar with each regimen, except that sleeplessness was less common with monthly dexamethasone (low-quality evidence) as was moon facies (moon-shaped appearance of the face) (moderate-quality evidence).Experience from large non-randomised studies suggests that corticosteroids are beneficial, but long-term use causes serious side effects.
AUTHORS' CONCLUSIONS: We are very uncertain about the effects of oral prednisone compared with no treatment, because the quality of evidence from the only RCT that exists is very low. Nevertheless, corticosteroids are commonly used in practice, supported by very low-quality evidence from observational studies. We also know from observational studies that corticosteroids carry the long-term risk of serious side effects. The efficacy of high-dose monthly oral dexamethasone is probably little different from that of daily standard-dose oral prednisolone. Most side effects occurred with similar frequencies in both groups, but with high-dose monthly oral dexamethasone moon facies is probably less common and sleeplessness may be less common than with oral prednisolone. We need further research to identify factors that predict response.
BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a disease that causes progressive or relapsing and remitting weakness and numbness. It is probably caused by an autoimmune process. Immunosuppressive or immunomodulatory drugs would be expected to be beneficial. This review was first published in 2003 and has been updated most recently in 2016.
OBJECTIVES: To assess the effects of immunomodulatory and immunosuppressive agents other than corticosteroids, immunoglobulin, and plasma exchange in CIDP.
SEARCH METHODS: On 24 May 2016, we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 4) in the Cochrane Library, MEDLINE, Embase, CINAHL, and LILACS for completed trials, and clinical trial registers for ongoing trials. We contacted the authors of the trials identified and other disease experts seeking other published and unpublished trials.
SELECTION CRITERIA: We sought randomised and quasi-randomised trials of all immunosuppressive agents, such as azathioprine, cyclophosphamide, methotrexate, ciclosporin, mycophenolate mofetil, and rituximab, and all immunomodulatory agents, such as interferon (IFN) alfa and IFN beta, in participants fulfilling standard diagnostic criteria for CIDP. We included all comparisons of these agents with placebo, another treatment, or no treatment.
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We wanted to measure the change in disability after one year as our primary outcome. Our secondary outcomes were change in disability after four or more weeks (from randomisation); change in impairment after at least one year; change in maximum motor nerve conduction velocity and compound muscle action potential amplitude after one year; and for participants who were receiving corticosteroids or intravenous immunoglobulin (IVIg), the amount of this medication given during at least one year after randomisation. Participants with one or more serious adverse events during the first year was also a secondary outcome.
MAIN RESULTS: Four trials fulfilled the selection criteria: one of azathioprine (27 participants), two of IFN beta-1a (77 participants in total) and one of methotrexate (60 participants). The risk of bias was considered low in the trials of IFN beta-1a and methotrexate but high in the trial of azathioprine. None of the trials showed significant benefit in any of the outcomes selected by their authors. The results of the outcomes which approximated most closely to the primary outcome for this review were as follows.In the azathioprine trial there was a median improvement in the Neuropathy Impairment Scale (scale range 0 to 280) after nine months of 29 points (range 49 points worse to 84 points better) in the azathioprine and prednisone treated participants compared with 30 points worse (range 20 points worse to 104 points better) in the prednisone alone group. There were no reports of adverse events.In a cross-over trial of IFN beta-1a with 20 participants, the treatment periods were 12 weeks. The median improvement in the Guy's Neurological Disability Scale (range 1 to 10) was 0.5 grades (interquartile range (IQR) 1.8 grades better to zero grade change) in the IFN beta-1a treatment period and 0.5 grades (IQR 1.8 grades better to 1.0 grade worse) in the placebo treatment period. There were no serious adverse events in either treatment period.In a parallel group trial of IFN beta-1a with 67 participants, none of the outcomes for this review was available. The trial design involved withdrawal from ongoing IVIg treatment. The primary outcome used by the trial authors was total IVIg dose administered from week 16 to week 32 in the placebo group compared with the IFN beta-1a groups. This was slightly but not significantly lower in the combined IFN beta-1a groups (1.20 g/kg) compared with the placebo group (1.34 g/kg, P = 0.75). There were four participants in the IFN beta-1a group and none in the placebo group with one or more serious adverse events, risk ratio (RR) 4.50 (95% confidence interval (CI) 0.25 to 80.05).The methotrexate trial had a similar design involving withdrawal from ongoing corticosteroid or IVIg treatment. At the end of the trial (approximately 40 weeks) there was no significant difference in the change in the Overall Neuropathy Limitations Scale, a disability scale (scale range 0 to 12), the median change being 0 (IQR −1 to 0) in the methotrexate group and 0 (IQR −0.75 to 0) in the placebo group. These changes in disability might have been confounded by the reduction in corticosteroid or IVIg dose required by the protocol. There were three participants in the methotrexate group and one in the placebo with one or more serious adverse events, RR 3.56 (95% CI 0.39 to 32.23).
AUTHORS' CONCLUSIONS: Low-quality evidence from randomised trials does not show significant benefit from azathioprine or interferon beta-1a and moderate-quality evidence from one randomised trial does not show significant benefit from a relatively low dose of methotrexate for the treatment of CIDP. None of the trials was large enough to rule out small or moderate benefit. The evidence from observational studies is insufficient to avoid the need for randomised controlled trials to discover whether these drugs are beneficial. Future trials should have improved designs, more sensitive outcome measures relevant to people with CIDP, and longer treatment durations.
OBJETIVO: Evaluar las pruebas sobre la eficacia de la inmunoglobulina IV (IgIV) para el tratamiento de trastornos neuromusculares.
MÉTODOS: El MEDLINE, Web of Science, y bases de datos EMBASE (1966 a 2009). Artículos seleccionados fueron clasificados de acuerdo a la Academia Americana de clasificación terapéutica de Neurología del esquema de pruebas; recomendaciones se basan en el nivel de evidencia.
RESULTADOS Y RECOMENDACIONES: IgIV es tan eficaz como la plasmaféresis y deben ser ofrecidas para el tratamiento del síndrome de Guillain-Barré (GBS) en adultos (Nivel A). IgIV es efectiva y debe ofrecerse en el tratamiento a largo plazo de polineuropatía desmielinizante inflamatoria crónica (Nivel A). IgIV es probablemente eficaz y debe ser considerado para tratar los dolores moderados a severos miastenia grave y neuropatía motora multifocal (nivel B). IgIV es posiblemente eficaz y se puede considerar para el tratamiento de la dermatomiositis nonresponsive en adultos y síndrome de Lambert-Eaton (Nivel C). La evidencia es insuficiente para apoyar o refutar el uso de la IgIV en el tratamiento de la neuropatía inmunoglobulina M paraproteína asociada, miositis por cuerpos de inclusión, polimiositis, radiculoplexoneuropathy diabética, o el síndrome de Miller Fisher, o en el tratamiento del síndrome postpolio rutina o en los niños con SGB (Nivel U). IgIV combinado con plasmaféresis no debe ser considerado para el tratamiento de EGB (Nivel B). Se necesitan más datos respecto a la eficacia de IgIV en comparación con otras combinaciones de tratamientos / tratamiento. La mayoría de los estudios concluyeron efectos adversos graves relacionados con IgIV-eran raros. Dada la naturaleza variable de estas enfermedades, tratamientos individualizados en función de las necesidades del paciente y el juicio del médico son importantes.
ANTECEDENTES: Teniendo en cuenta el creciente uso de la inmunoglobulina intravenosa (IGIV) para diversas enfermedades neurológicas y la incertidumbre relacionados con sus beneficios y los daños, una revisión sistemática se llevó a cabo de ensayos controlados aleatorios (ECA) que evaluaron la IGIV para todas las indicaciones neurológicas para las que no estaba en por lo menos una prueba publicada.
Materiales y métodos: Para esta revisión sistemática, una estrategia de búsqueda sistemática se aplicó a MEDLINE (1966-junio de 2003) y el Registro Cochrane de Ensayos Controlados (junio de 2003) para identificar ECA potencialmente elegibles que compararon IgIV con placebo o un control activo. Todos los regímenes de dosificación fueron considerados. Los resúmenes se excluyeron, y no hubo restricciones de idioma de publicación. Dos investigadores independientes realizaron la extracción de datos con un formulario estandarizado. Medidas del efecto se calcularon para cada ensayo de forma independiente, y los estudios se agruparon según el criterio clínico y metodológico en cuanto a su idoneidad. Cuando la puesta en común de los ensayos fue la adecuada, un análisis cualitativo de los resultados se proporciona.
Resultados y conclusiones: Treinta y siete ensayos que representan a 14 condiciones fueron identificados. Inmunoglobulina intravenosa es más eficaz que el placebo para el tratamiento de recaída-remisión de esclerosis múltiple y la idiopática polineuropatía desmielinizante inflamatoria crónica. También existe un beneficio potencial para el tratamiento de la neuropatía motora multifocal, miastenia gravis, dermatomiositis, síndrome de persona rígida, y de Lambert-Eaton síndrome miasténico. No hubo pruebas suficientes para determinar si la terapia de inmunoglobulina intravenosa fue más eficaz que el intercambio de plasma para el síndrome de Guillain-Barré. También hubo pruebas suficientes en relación con paraproteína asociada a polineuropatía. No hay evidencia de beneficio se observó para la esclerosis múltiple secundaria progresiva o miositis por cuerpos de inclusión.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a progressive or relapsing and remitting paralysing illness, probably due to an autoimmune response, which should benefit from corticosteroid treatment. Non-randomised studies suggest that corticosteroids are beneficial. Two commonly used corticosteroids are prednisone and prednisolone. Both are usually given as oral tablets. Prednisone is converted into prednisolone in the liver so that the effect of the two drugs is usually the same. Another corticosteroid, dexamethasone, is more potent and is used in smaller doses. The review was first published in 2001 and last updated in 2015; we undertook this update to identify any new evidence.
OBJECTIVES:
To assess the effects of corticosteroid treatment for CIDP compared to placebo or no treatment, and to compare the effects of different corticosteroid regimens.
SEARCH METHODS:
On 8 November 2016, we searched the Cochrane Neuromuscular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for randomised trials of corticosteroids for CIDP. We searched clinical trials registries for ongoing trials.
SELECTION CRITERIA:
We included randomised controlled trials (RCTs) or quasi-RCTs of treatment with any corticosteroid or adrenocorticotrophic hormone for CIDP, diagnosed by an internationally accepted definition.
DATA COLLECTION AND ANALYSIS:
Two authors extracted data from included studies and assessed the risk of bias independently. The intended primary outcome was change in disability, with change in impairment after 12 weeks and side effects as secondary outcomes. We assessed strength of evidence using the GRADE approach.
MAIN RESULTS:
One non-blinded RCT comparing prednisone with no treatment in 35 eligible participants did not measure the primary outcome for this systematic review. The trial had a high risk of bias. Neuropathy Impairment Scale scores after 12 weeks improved in 12 of 19 participants randomised to prednisone, compared with five of 16 participants randomised to no treatment (risk ratio (RR) for improvement 2.02 (95% confidence interval (CI) 0.90 to 4.52; very low-quality evidence). The trial did not report side effects in detail, but one prednisone-treated participant died.A double-blind RCT comparing daily standard-dose oral prednisolone with monthly high-dose oral dexamethasone in 40 participants reported none of the prespecified outcomes for this review. The trial had a low risk of bias, but the quality of evidence was limited as it came from a single small study. There was little or no difference in number of participants who achieved remission (RR 1.11; 95% CI 0.50 to 2.45 in favour of monthly dexamethasone; moderate-quality evidence), or change in disability or impairment after one year (low-quality evidence). Change of grip strength or Medical Research Council (MRC) scores demonstrated little or no difference between groups (moderate-quality to low-quality evidence). Eight of 16 people in the prednisolone group and seven of 24 people in the dexamethasone group deteriorated. Side effects were similar with each regimen, except that sleeplessness was less common with monthly dexamethasone (low-quality evidence) as was moon facies (moon-shaped appearance of the face) (moderate-quality evidence).Experience from large non-randomised studies suggests that corticosteroids are beneficial, but long-term use causes serious side effects.
AUTHORS' CONCLUSIONS:
We are very uncertain about the effects of oral prednisone compared with no treatment, because the quality of evidence from the only RCT that exists is very low. Nevertheless, corticosteroids are commonly used in practice, supported by very low-quality evidence from observational studies. We also know from observational studies that corticosteroids carry the long-term risk of serious side effects. The efficacy of high-dose monthly oral dexamethasone is probably little different from that of daily standard-dose oral prednisolone. Most side effects occurred with similar frequencies in both groups, but with high-dose monthly oral dexamethasone moon facies is probably less common and sleeplessness may be less common than with oral prednisolone. We need further research to identify factors that predict response.
